D. C. W. and, C. Mason
Feb 24, 1998
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0
Influential Citations
9
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Journal
Organic Process Research & Development
Abstract
A regioselective Heck cross-coupling strategy is presented for the large-scale preparation of the thromboxane receptor antagonist 3-{3-[2-(4-chlorobenzenesulfonamido)ethyl]-5-(4-fluorobenzyl)phenyl}propionic acid (1). Commercially available 3-bromo-5-iodobenzoic acid was first converted to the corresponding acid chloride, and this was then condensed with 4-fluorobenzene via a Friedel−Crafts acylation reaction to give 3-bromo-5-iodophenyl 4-fluorophenyl ketone. Regioselective cross-coupling with ethyl acrylate and then N-vinylphthalimide, each under phosphine-free Heck conditions, led to formation of ethyl 3-[3-(4-fluorobenzoyl)-5-(2-phthalimidovinyl)phenyl]propenoate. Reduction of the benzophenone moiety and saturation of the olefin double bonds, followed by phthalimide ring cleavage, then gave ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propionate monocitrate salt. This was converted to the sulfonamido-substituted arylpropionic acid 1 via a two-step one-pot procedure in which sulfonamide formation...